In developing humans and other mammals, not all genes are created equal – or equally used. The expression of certain genes, known as imprinted genes, is determined by just one copy of the parents’ genetic contribution. In humans, there are at least 80 known imprinted genes. If a copy of an imprinted gene fails to function correctly – or if both copies are expressed – the result can be a variety of heritable conditions, such as Prader-Willi and Angelman syndromes, or increased risk for cancer.
DNA Methylation is a common way cells turn genes “off” in imprinted genes, resulting in only one of the two copies of the gene being expressed. To study the mechanism of imprinted genes in mouse brain, Xie et al. generated a whole-genome, base-resolution map of allelic DNA methylation in the frontal cortex. The study identified many genomic regions that are differentially methylated, dependent on the parent-of-origin. They also discovered sequence signatures correlated with CG methylation that are evolutionarily conserved as well as previously unknown genes that are subject to imprinting, including micro RNAs. The most surprising finding was significant amounts of methylation outside of the CG dinucleotide context (non-CG) in the brain. This epigenetic mark previously documented only in embryonic stem cells, preimplantation embryos and oocytes, was thought to be a marker of pluripotency, which is the capacity to become many types of cells. The significance of non-CG methylation is unknown, however the presence of this mark in brain is very specific, suggesting that it correlates with an important biological function
Original Scientific Publication: Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Xie W, Barr CL, Kim A, Yue F, Lee AY, Eubanks J, Dempster EL, Ren B. Cell 148(4): 816-831, 2012.
Source of text: C. Barr, University of Toronto
